Mepron and Coconut Oil May Not Be A Good Idea Afterall

PUBMED said...
Examination of some factors responsible for a food-induced increase in absorption of atovaquone.
Rolan PE1, Mercer AJ, Weatherley BC, Holdich T, Meire H, Peck RW, Ridout G, Posner J.

1. Atovaquone is a potent antiprotozoal slowly and irregularly absorbed after administration as tablets to fasting volunteers. A series of studies was performed to investigate the effects of food, bile and formulation on atovaquone absorption. 2. In 18 healthy male volunteers, a high-fat breakfast administered 45 min before 500 mg atovaquone as tablets increased AUC by 3.3-fold (95% CI 2.8-4.0) and Cmax 5.3-fold (4.3-6.6) compared with fasting. 3. The absorption of atovaquone from tablets was examined in 12 healthy male volunteers after an overnight fast, following toast alone, toast with 28 g butter (LOFAT), or toast with 56 g butter (HIFAT). Compared with absorption when fasted, toast had no significant effect but LOFAT increased AUC 3.0-fold (2.1-4.2) and Cmax 3.9-fold (2.6-5.8). HIFAT increased AUC 3.9-fold (2.7-5.5) and Cmax 5.6-fold (3.8-8.4). 4. The absorption of atovaquone was examined in nine healthy fasting male volunteers from tablets, an aqueous suspension, and an oily solution/suspension in miglyol (fractionated coconut oil). Compared with tablets, AUC following the aqueous suspension was increased 1.7-fold (1.0-2.7) and Cmax 2.4-fold (1.7-3.5). Following miglyol, AUC was increased to the same extent but Cmax was only increased 1.8-fold (1.2-2.6). 5. Atovaquone absorption was examined in eight healthy fasting male volunteers following an i.v. infusion of cholecystokinin octapeptide (CCK-OP) which decreased gallbladder volume by 82% (73%-90%) on occasion 1 or saline on occasion 2. AUC(0,12) was increased following CCK-OP by 1.6-fold (1.1-2.4) and Cmax by 1.5-fold (0.98-2.4).(ABSTRACT TRUNCATED AT 250 WORDS)

ASM said...
Atovaquone (566C80), a hydroxy-1,4-naphthoquinone, is a structural analog of protozoan ubiquinone, a mitochondrial protein involved in electron transport. It is a highly lipophilic molecule with very low aqueous solubility. Currently, atovaquone is marketed as Mepron (GlaxoSmithKline), a yellow crystalline solid in a citrus-flavored liquid suspension (750 mg of atovaquone/5 ml of suspension) (product information, Mepron [atovaquone] suspension, 1999, GlaxoWellcome). When atovaquone was first released in 1992 it was as a tablet, but this formulation was discontinued because of poor and unreliable bioavailability (102). The drug was reformulated as a micronized suspension with small particle size that allowed improved absorption compared with that of the tablet. Atovaquone levels in blood are doubled when it is ingested with food containing significant fats and reach steady-state concentrations of 15 to 30 μg/ml with doses of 750 to 1,500 mg (6, 29, 102; product information, Mepron [atovaquone] suspension, 1999, GlaxoWellcome).